This ROO transition application on the development of optical methods for imaging transient structural changes associated with neural activity integrates rigorous physics, biomedical, and neuroscience research to further the research goals of the original K99/R00 proposal. The mentored (K99) phase has allowed Dr. B. Hyle Park a successful transition to an independent research positioii in the Bioengineering department at the University of California, Riverside. The parameters of the position provide for start-up funding, space, and support that are comparable or exceed that of other recently hired faculty. Furthermore^ it also provides for at least 75% protected research time with a generous amount of teaching relief. The independent (ROO) phase will further Dr. Park's development as an independent researcher and facilitate successful application for an independent research grant (ROl). Having completed his graduate research in physics with a strong focus on biomedical imaging, particularly in the development and clinical application of polarization-sensitive optical coherence tomo^phy, Dr. Park has complemented this grounding in biomedical optics with coursework in and hands-on laboratoiy experience with current neuroscience techniques. His research proposal addresses the need for non-contact detection of neural structure and activity. Current techniques for detection of action potential propagation involve direct contact with electrodes or introduction of chemical markers, such as Ca^^ dyes. The focus of this K99/R00 is optical detection of transient structural changes that accompany spike propagation in neurons using a phasesensitive interferometric technique known as spectral-domain optical coherence tomography (SD-OCT). An important first step in optically detecting activity in nerves is the ability to identify them in SD-OCT images. During the mentored (K99) phase, it was shown that unmyelinated limulus lateral compound optic nerve and myelinated rat sciatic nerve can be idientifled fiom surrounding other tissue types in structural images, providing valuable groundwork for future in vivo application of optical detection of neural activity as it allows for differentiation of myelinated and non-myelinated neurons versus other tissue types within acquired images. These results also demonstrate that quantitative analysis of optical images of nerve structure is capable of non-destructive assessment of the degree of nerve myelination. A correlation between electrically recorded action potential propagation with optical detection of associated axonal thickness changes was established, and such detection is possible for single impulses without requiring averaging of results from repeated trials. The independent phase ofthis propos^ aims to further develop this optical technique such that it can be applied to detailed studies of the interaction between individual cells in and behavior of functional neural networks. Successful completion of the proposed research will enable optical detection of the structure and activity of nerves and neuronal ensembles in vilro, and lay the groundwork for in vivo application as well as providing the preliminary results necessary fbr a successful ROI application. This work not only has potential ^plication as a complement to electrophysiology, but would be of use where optical detection could be siibstituted where introduction of a large number of electrodes can be problematic and in clinically important regions, such as the retina, that are largely inaccessible with current techniques.